Paquot N, Schneiter P, Jéquier E, Gaillard R, Lefèbvre P J, Scheen A, Tappy L
Départment of Médecine, CHU Sart Tilman, Liège, Belgium.
Diabetologia. 1996 May;39(5):580-6. doi: 10.1007/BF00403305.
Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C fructose (0.3 g.kg fat free mass-1.h-1) for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM (17.7 +/- 1.9 mumol.kg fat free mass-1.min-1 basal vs 15.9 +/- 0.9 after fructose), in obese non-diabetic subjects (12.1 +/- 0.5 basal vs 13.1 +/- 0.5 after fructose) and in lean healthy subjects (13.3 +/- 0.5 basal vs 13.8 +/- 0.6 after fructose) although 13C glucose synthesis contributed 73.2% of EGP in lean subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose ingestion + hyperglucagonaemia (232 +/- 9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8% with ingestion of fructose + glucagon (p < 0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i.e. glycogenolysis + gluconeogenesis from non-fructose precursors).
内源性葡萄糖生成（EGP）增加和糖异生作用促成了非胰岛素依赖型糖尿病（NIDDM）患者高血糖的发病机制。然而，在健康受试者中，给予糖异生前体时EGP保持恒定。本研究旨在确定给予果糖是否会增加肥胖NIDDM患者和肥胖非糖尿病受试者的EGP。对8名年轻健康瘦人、8名中年肥胖NIDDM患者和7名中年肥胖非糖尿病受试者进行了研究，他们在3小时内每小时摄入13C果糖（0.3 g·kg去脂体重-1·h-1）。果糖未能增加NIDDM患者（基础值17.7±1.9 μmol·kg去脂体重-1·min-1，果糖摄入后为15.9±0.9）、肥胖非糖尿病受试者（基础值12.1±0.5，果糖摄入后为13.1±0.5）和健康瘦人（基础值13.3±0.5，果糖摄入后为13.8±0.6）的EGP（用6,6 2H葡萄糖测量），尽管13C葡萄糖合成在健康瘦人中占EGP的73.2%，在肥胖非糖尿病受试者中占62.6%，在肥胖NIDDM患者中占52.8%。由于胰高血糖素可能在NIDDM患者高血糖的发生中起重要作用，因此还对健康受试者在摄入13C果糖+高胰高血糖素血症（232±9 ng/l）期间以及单独高胰高血糖素血症期间进行了研究。摄入果糖+胰高血糖素后EGP增加了19.8%（p<0.05），但单独给予果糖或胰高血糖素期间EGP保持不变。无论有无胰高血糖素，摄入果糖后血浆13C葡萄糖富集相同，表明在这两种情况下果糖糖异生对6-磷酸葡萄糖池的贡献相同。我们得出结论，在给予果糖期间：1）糖异生增加，但NIDDM患者、肥胖非糖尿病患者和瘦人个体的EGP保持恒定；2）在瘦人个体中，需要增加胰高血糖素血症和增加糖异生前体供应才能增加EGP；这种EGP的增加在果糖和其他来源（即糖原分解+非果糖前体的糖异生）产生6-磷酸葡萄糖的相对比例无变化的情况下发生。
